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Autologous Haematopoietic Stem Cell Transplantation (Ahsct) for Severe Resistant Autoimmune and Inflammatory Diseases - a Guide for the Generalist

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Autologous Haematopoietic Stem Cell Transplantation (Ahsct) for Severe Resistant Autoimmune and Inflammatory Diseases - a Guide for the Generalist This is a repository copy of Autologous haematopoietic stem cell transplantation (aHSCT) for severe resistant autoimmune and inflammatory diseases - a guide for the generalist. White Rose Research Online URL for this paper: http://eprints.whiterose.ac.uk/144052/ Version: Published Version Article: Snowden, J.A. orcid.org/0000-0001-6819-3476, Sharrack, B., Akil, M. et al. (5 more authors) (2018) Autologous haematopoietic stem cell transplantation (aHSCT) for severe resistant autoimmune and inflammatory diseases - a guide for the generalist. Clinical Medicine, 18 (4). pp. 329-334. ISSN 1470-2118 https://doi.org/10.7861/clinmedicine.18-4-329 © Royal College of Physicians 2018. This is an author produced version of a paper subsequently published in Clinical Medicine. Uploaded in accordance with the publisher's self-archiving policy. 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[email protected] https://eprints.whiterose.ac.uk/ Clinical Medicine 2018 Vol 18, No 4: 329–34 CME HAEMATOLOGY Autologous haematopoietic stem cell transplantation (aHSCT) for severe resistant autoimmune and inflammatory diseases – a guide for the generalist A u t h o r s : John A Snowden , A Basil Sharrack , B Mohammed Akil ,C D a v i d G K i e l y , D Alan Lobo , E M a j i d K a z m i , F P a o l o A M u r a r o G and James O Lindsay H Autologous haematopoietic stem cell transplantation (aHSCT) I n t r o d u c t i o n is commonly used for the treatment of haematological cancers, Haematopoietic stem cell transplantation (HSCT) has evolved but is increasingly used in the treatment of patients severely over the past 50 years to treat a wide range of conditions and is affected by autoimmune diseases (ADs). In fact, ADs have now a routine part of clinical haematological practice (Table 1 ). become the fastest growing indication for aHSCT. A wide range Autologous HSCT (aHSCT) is widely used to treat malignant ABSTRACT of diseases have been treated, but the field has focused on three diseases such as myeloma and lymphoma. With time, aHSCT has areas: multiple sclerosis, diffuse cutaneous systemic sclerosis become safer and its use has also extended to non-malignant and Crohn’s disease, where there are populations of patients diseases, including severe autoimmune diseases (ADs), which is for whom disease control remains unsatisfactory despite the now the fastest growing indication for HSCT. 1 advent of biological and targeted small molecule therapies. Clinical studies of aHSCT in ADs have been ongoing since the Scientific studies of immune reconstitution have provided mid-1990s. However, it has taken two decades for aHSCT to be support for a ‘rebooting’ of the immune system through a re-diversification of naive and regulatory immune effector cells. In addition, there may be health economic benefits from a single one-off procedure. Even so, the treatment with aHSCT Key points is intensive with a range of toxicities and risks which, despite being routine to transplant haematologists, are less familiar Autologous HSCT has the potential to induce sustained clinical to disease specialists. Close collaboration between transplant remissions in otherwise resistant or poor prognosis autoimmune haematologists and relevant disease specialists in patient diseases enabling reduction and even long-term withdrawal of selection, clinical management and follow-up is mandatory. immunosuppressive and biological therapies Ideally, patients should be treated on a clinical trial if available. Although a wide range of autoimmune diseases have been treated, the evidence base is greatest in relapsing remitting MS, diffuse systemic sclerosis and Crohn’s disease A u t h o r s : A c o n s u l t a n t h a e m a t o l o g i s t , d i r e c t o r o f B M T a n d c h a i r o f the Autoimmune Diseases Working Party (ADWP) of the European Autologous HSCT requires close collaboration between Society for Blood and Marrow Transplantation (EBMT), Department of experienced transplant haematologists and relevant disease Haematology, Sheffield Teaching Hospitals NHS Foundation Trust, Royal specialists in patient selection, management and follow- B Hallamshire Hospital, Sheffield, UK ; consultant neurologist, Department up. Early referral of patients is essential to optimise clinical of Neurology, Sheffield Teaching Hospitals NHS Foundation Trust, outcomes and minimise risks Royal Hallamshire Hospital, Sheffield, UK ; C consultant rheumatologist, Department of Rheumatology, Sheffield Teaching Hospitals NHS Autologous HSCT may lead to ‘rebooting’ of the immune D Foundation Trust, Royal Hallamshire Hospital, Sheffield, UK ; consultant system through regeneration and rediversification of the T and respiratory physician, Sheffield Pulmonary Vascular Disease Unit, B-cell repertoire and increased regulatory T-cell activity Sheffield Teaching Hospitals NHS Foundation Trust, Royal Hallamshire E Hospital, Sheffield, UK ; c o n s u l t a n t g a s t r o e n t e r o l o g i s t , D e p a r t m e n t o f There may be health economic benefits to a one-off intensive Gastroenterology, Sheffield Teaching Hospitals NHS Foundation Trust, treatment over long-term administration of biological and F Royal Hallamshire Hospital, Sheffield, UK ; consultant haematologist, immunosuppressive therapy Kings Healthcare Partners, London, UK ; G professor of neurology, neuroimmunology and immunotherapy, Brain Sciences, Imperial College KEYWORDS: Autoimmune diseases, haematopoietic stem cell H London, London, UK ; professor of inflammatory bowel disease, Centre transplantation, stem cells, autologous, blood and marrow for Immunobiology, Barts and the London School of Medicine and transplantation I Dentistry, Blizard Institute, Queen Mary University of London, London, UK © Royal College of Physicians 2018. All rights reserved. 329 CME Haematology Table 1. Glossary of terms used in haematopoietic recognised as a treatment option among the evolving array of biologic and other modern therapies. More recent evidence has stem cell transplantation (HSCT) supported its use in well-selected patients with ADs, especially Types of HSCT multiple sclerosis (MS), systemic sclerosis (SSc) and Crohn’s disease 2,3 Autologous Transplantation of haematopoietic stem cells (CD). Consensus recommendations have been published to guide judicious patient selection and multidisciplinary practice of HSCT (aHSCT) taken from patients and reinfused after high 4–8 doses of cytotoxic therapy (usually chemotherapy aHSCT across a range of ADs. with immunoablative therapeutic antibodies such as anti-thymocyte globulin [ATG] in patients with Multiple sclerosis severe autoimmune diseases) Current disease modifying therapies (DMTs) reduce relapse rates Allogeneic Transplantation of haematopoietic stem cells in patients with relapsing remitting MS (RRMS) but their impact on HSCT from a donor, either sibling or unrelated, and disability is limited. DMTs for progressive MS are scarcely effective occasionally cord blood. Allogeneic HSCT is and early intervention at the inflammatory RRMS phase of this rarely performed for autoimmune diseases illness is therefore key to preventing long-term disability. 9 – 11 given the higher risks, and its use has been Autologous haematopoietic stem cell transplantation has been largely restricted to paediatrics used in the treatment of MS since 1995. Initially, patients with 9–11 Sources of haematopoietic stem cells (HSC) advanced progressive disease were treated with limited benefit. A small phase II randomised controlled trial (RCT) confirmed Peripheral Stem cells, labelled by the antigen CD34+, are reduced magnetic resonance imaging (MRI) disease activity blood stem mobilised using granulocyte colony stimulating with aHSCT,12 which strongly supported further phase III studies cells factor (G-CSF) +/− chemotherapy from the with primary clinical endpoints. There is now increasing evidence bone marrow into the blood then harvested that its early use in patients with highly active RRMS results in with apheresis significant reduction in clinical and MRI disease activity as well Bone marrow Haematopoietic stem cell source derived by direct as improving patients’ disability to a significantly greater degree aspiration of bone marrow, a stem cell source compared with currently available DMTs. 9 – 11 The recent results infrequently used now for autologous HSCT of the MIST study (ClinicalTrials.gov identifier: NCT00273364), HSCT phases which compared the effectiveness of aHSCT against standard DMTs, suggests that aHSCT can be safely administered and is Mobilisation Mobilisation of CD34+ stem cells from the significantly more effective. 13 However, alemtuzumab, one of the bone marrow into the peripheral blood using most effective DMTs, was not included in the control arm. An RCT granulocyte colony stimulating factor (G-CSF) +/− of aHSCT with alemtuzumab would resolve the question of relative chemotherapy. Stem cells are then harvested using efficacy. leukapheresis
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